Neonatal Abstinence Syndrome and High School Performance.

BACKGROUND AND OBJECTIVES: Little is known of the long-term, including school, outcomes of children diagnosed with Neonatal abstinence syndrome (NAS) (International Statistical Classification of Disease and Related Problems [10th Edition], Australian Modification, P96.1). METHODS: Linked analysis of health and curriculum-based test data for all children born in the state of New South Wales (NSW), Australia, between 2000 and 2006. Children with NAS (n = 2234) were compared with a control group matched for gestation, socioeconomic status, and gender (n = 4330, control) and with other NSW children (n = 598 265, population) for results on the National Assessment Program: Literacy and Numeracy, in grades 3, 5, and 7. RESULTS: Mean test scores (range 0-1000) for children with NAS were significantly lower in grade 3 (359 vs control: 410 vs population: 421). The deficit was progressive. By grade 7, children with NAS scored lower than other children in grade 5. The risk of not meeting minimum standards was independently associated with NAS (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 2.2-2.7), indigenous status (aOR, 2.2; 95% CI, 2.2-2.3), male gender (aOR, 1.3; 95% CI, 1.3-1.4), and low parental education (aOR, 1.5; 95% CI, 1.1-1.6), with all Ps < .001. CONCLUSIONS: A neonatal diagnostic code of NAS is strongly associated with poor and deteriorating school performance. Parental education may decrease the risk of failure. Children with NAS and their families must be identified early and provided with support to minimize the consequences of poor educational outcomes.

Epidemiological Evidence for a Decreasing Incidence of Neonatal Abstinence Syndrome, 2000-11.

BACKGROUND: This study analyses the incidence of Neonatal Abstinence Syndrome (NAS) in a large geographically defined population in Australia. METHOD: Database linkage analysis of all births between 2000 and 2011 in New South Wales (NSW), Australia. The diagnosis of NAS was derived from hospital coding P96.1, 'Neonatal withdrawal symptoms from maternal use of drugs of addiction'. Temporal trends were studied by comparing epoch 1 (2000-05) with epoch 2 (2006-11). The relationship with changes in maternal factors was further analysed. RESULTS: The NAS was coded in 3842 of 1 022 263 live born infants (0.38%). NAS incidence peaked at 5.07 per 1000 live births in 2002, decreasing to 3.18 in 2011 and was negatively correlated with maternal age (r = -0.7). The rate of NAS in epoch 2 (3.4 per 1000 births, 95% CI 3.28, 3.58) was significantly lower than in epoch 1 (4.1 per 1000 births, 95% CI 3.96, 4.33). Epoch 2 mothers were significantly older (mean 29.8 years vs. 28.3 years), less likely to be multiparous (OR 0.7, 95% CI 0.6, 0.9) or smoke (OR 0.4, 95% CI 0.4, 0.5). They were more likely to engage in antenatal care earlier (mean first visit: 14.1 vs. 18.9 weeks). Most infants (~80%) were born at term (>37 weeks gestation). CONCLUSION: The incidence of NAS as a discharge diagnosis has decreased in our population since 2002. Mothers are also older and engaging earlier in prenatal care. Whether these changes alter NAS presentation and diagnosis or whether pregnant women are using drugs that do not cause typical NAS (e.g. amphetamines) is uncertain and requires further study.

Reasons for Rehospitalization in Children Who Had Neonatal Abstinence Syndrome.

BACKGROUND AND OBJECTIVES: Neonatal abstinence syndrome (NAS) occurs after in utero exposure to opioids, but outcomes after the postnatal period are unclear. Our objectives were to characterize childhood hospitalization after NAS. METHODS: Population-based linkage study of births, hospitalization, and death records of all children registered in New South Wales (NSW), Australia, between 2000 and 2011 to a maximum of 13 years. Infants with an International Statistical Classification of Disease and Related Problems, 10th Edition, Australian Modification, coding of NAS (P96.1, n = 3842) were compared with 1,018,421 live born infants without an NAS diagnosis. RESULTS: Infants with NAS were more likely to be admitted into a nursery (odds ratio 15.6, 95% confidence interval: 14.5-16.8) and be hospitalized longer (10.0 vs 3.0 days). In childhood, they were more likely to be rehospitalized (1.6, 1.5-1.7), die during hospitalization (3.3, 2.1-5.1), and be hospitalized for assaults (15.2, 11.3-20.6), maltreatment (21.0, 14.3-30.9), poisoning (3.6, 2.6-4.8), and mental/behavioral (2.6, 2.1-3.2) and visual (2.9, 2.5-3.5) disorders. Mothers of infants with NAS were more likely to be Indigenous (6.4, 6.0-7.0), have no antenatal care (6.6, 5.9-7.4), and be socioeconomically deprived (1.6, 1.5-1.7). Regression analyses demonstrated that NAS was the most important predictor of admissions for maltreatment (odds ratio 4.5, 95% confidence interval: 3.4-6.1) and mental and behavioral disorders (2.3, 1.9-2.9), even after accounting for prematurity, maternal age, and Indigenous status. CONCLUSIONS: Children with NAS are more likely to be rehospitalized during childhood for maltreatment, trauma, and mental and behavioral disorders even after accounting for prematurity. This continues to adolescence and emphasizes the critical need for continued support of this vulnerable group after resolution of NAS.

Perinatal outcomes of Australian buprenorphine-exposed mothers and their newborn infants.

AIM: To determine the short-term outcomes of Australian buprenorphine-exposed mother/infant dyads. METHODS: Retrospective record review of drug-exposed mothers and infants in Australia. Groups were based on drug exposure: buprenorphine (55, 3.8%), non-buprenorphine opiates (O, 686, 48.6%) and non-opiates (NO, 671, 47.5%). RESULTS: More than 30% of buprenorphine mothers continued to use heroin (21, 38%) and benzodiazepines (16, 29%). They were more likely to have child at risk concerns (29, 52.7%, P = 0.019) and have previous children placed in out-of-home care (9, 16.3%, P = 049). Buprenorphine babies were less likely to be preterm (16% vs. 25% (O), P = 0.001 and 23% (NO), P = 0.004) and had higher birthweights (median: 3165 g vs. 2842.5 g (O), P < 0.001 and 2900 g (NO), P = 0.004). Buprenorphine and non-buprenorphine opioid babies had similar maximum Finnegan scores (median 10 vs. 11(O), P = 0.144). The number of babies needing abstinence treatment (45% vs. 51% (O), P = 0.411) and length of hospital stay (median days 9 vs. 11(O), P = 0.067) were similar, but buprenorphine infants required lower maximum morphine doses (mg/kg/day) (median 0.4 mg vs. 0.5 mg (O), P = 0.009). CONCLUSIONS: Short-term medical outcomes of infants of buprenorphine-using mothers are similar to those of non-buprenorphine opiate-using mothers, but interpretation of these results is confounded by the high rates of polydrug exposure in the buprenorphine group. This and other social concerns noted in buprenorphine mothers and infants warrant further study.

Dopamine D2 receptor gene polymorphisms in newborn infants of drug-using women.

OBJECTIVES: To determine the characteristics of dopamine D2 receptor gene (DRD2) polymorphisms in drug-exposed and unexposed neonates and the relationship to neonatal abstinence syndrome (NAS). DESIGN: Retrospective case-control analysis between drug-exposed and unexposed infants between DRD2 polymorphisms, drug exposure and NAS treatment. PATIENTS: Drug-exposed (n=48) and drug-free (n=49) infants born between March 1999 and December 2006. METHODS: Analysis of DNA for the Taq1A, -141Ins/Del and Ser311Cys DRD2 polymorphisms. Drug exposure was determined by antenatal maternal drug and alcohol history. Frequency measures of DRD2 polymorphisms were compared between drug-exposed infants, treatment NAS medication and with control infants. SETTING: Tertiary maternity hospital, Sydney, Australia. MAIN OUTCOME MEASURES: All infants were born in a good condition (25.7% <37 weeks gestation). Opiates (methadone and heroin) were used by 45 (93.8%) of drug-exposed mothers. The A2A2 allele was more common in drug-exposed infants (37 (77.0%) versus 23 (46.9%), p=0.003) but the A1A2 allele was more common in control infants (23 (46.9%) versus 4 (8.3%), p=0.00002). The-ins allele was more common in control (39 (79.6%) versus 20 (41.7%), p=<0.01) and unmedicated drug-exposed (14/25 (56%) versus 5/23 (21.7%), p=0.02) infants. The majority of infants (41 (83.7%) controls versus 41 (85.4%), p=1.000) expressed the least common, Ser polymorphism. CONCLUSIONS: DRD2 polymorphisms are detectable from DNA obtained from stored blood spots. The -ins allele is more common in control and unmedicated drug-exposed infants. Further study is recommended to explore postneonatal outcomes especially in relation to neuropsychiatric behaviours.

The temporal influence of a heroin shortage on pregnant drug users and their newborn infants in Sydney, Australia.

BACKGROUND: Heroin availability and purity decreased precipitously in Australian markets between 2000 and 2001. This led to increased use of non-opiate drugs in the general community but whether pregnant drug users and their newborn infants were affected remains unknown. AIM: To determine if perinatal drug exposure and outcomes are affected by changes in street drug availability. METHODS: Retrospective review was carried out of known drug-exposed mothers delivering live-born infants at the Royal Hospital for Women, Randwick, Australia (n = 316). Study periods were divided into preshortage (A = 1998-2000, n = 79), shortage (B = 2001-2002, n = 92) and post-shortage (C = 2003-2006, n = 122) periods. Cannabis-only users were excluded (n = 23). RESULTS: The percentage of confined women who admitted to using heroin decreased significantly (65%(A) vs 34%(B), P < 0.01) as did women on methadone programmes (90%(A), 80%(B), 75%(C), P = 0.024). The use of cocaine (7% (A) vs 33% (B), P = 0.031) and amphetamines (4% (A) vs 22% (C), P = 0.01), tripled. Most infants were born full-term and healthy but the duration of infant hospitalisation increased significantly from (median [interquartile range]) 8 [10, 38](A) to 13 [7, 23](C) days (P < 0.01). Approximately 50% of infants required withdrawal treatment but more needed phenobarbitone as an adjunct to morphine during the shortage (4/80 (0.5%) vs 15/93 (16%), P = 0.026), probably because of increased exposure to non-opiate drugs. CONCLUSIONS: The types of drugs used by pregnant drug users follow street trends and may affect infant hospitalisation and withdrawal treatment. Of concern is the rise in amphetamine-use and there needs to be increased vigilance for similar trends, especially in previously unidentified drug users.

Growth-promoting effect of Rh(D) antibody on human pancreatic islet cells.

CONTEXT/OBJECTIVE: Hyperinsulinism with islet cell hyperplasia is a frequent complication, of unknown cause, in hemolytic disease of the newborn, occurring in Rh(D)-positive infants of Rh-isoimmunized Rh(D)-negative mothers, but not in infants with other hemolytic disorders. We investigated the possibility that trans-placentally acquired anti-D Ig is the cause of both conditions. DESIGN: Monolayer cultures of human islet cells were exposed to sera from Rh-isoimmunized mothers and newborns, where jaundice, hyperinsulinism, and hypoglycemia in the infant had ensued. Parallel cultures with anti-D, specific anti-D monoclonal antibodies, normal human Ig (15 microg/ml), and serum controls were also undertaken. Islet cell proliferation was determined by [3H]thymidine incorporation. Insulin storage and chronic and acute insulin secretion to glucose were analyzed by RIA. Rh(D) surface antigen expression was determined on islet cells by flow cytometric analysis. RESULTS: Islet cell proliferation and insulin secretion were significantly greater in coculture with test sera (P < 0.01; n = 8) and with anti-D (P < 0.001; n = 8), compared with either controls or Ig. After 8 d of growth, the static incubation experiment showed a 3.5-fold response to glucose stimulus in all sera. Rh(D) antigen expression was detected on the islet cell surface by flow cytometry, and islet cell morphology was normal. Colocalization of the proliferation marker Ki67 with insulin by immunofluorescent staining further indicated that Rh(D) antibody promoted islet growth. CONCLUSIONS: The anti-Rh(D) islet cell proliferative effect generates neonatal hyperinsulinism in Rh isoimmunization. Anti-Rh(D) may have application for islet cell proliferation in diabetes mellitus treatment for Rh(D)-positive subjects. Further analysis is required.